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Title: Structural and genetic convergence of HIV-1 neutralizing antibodies in vaccinated non-human primates

Journal Article · · PLoS Pathogens
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A primary goal of HIV-1 vaccine development is the consistent elicitation of protective, neutralizing antibodies. While highly similar neutralizing antibodies (nAbs) have been isolated from multiple HIV-infected individuals, it is unclear whether vaccination can consistently elicit highly similar nAbs in genetically diverse primates. Here, we show in three outbred rhesus macaques that immunization with Env elicits a genotypically and phenotypically conserved nAb response. From these vaccinated macaques, we isolated four antibody lineages that had commonalities in immunoglobulin variable, diversity, and joining gene segment usage. Atomic-level structures of the antigen binding fragments of the two most similar antibodies showed nearly identical paratopes. The Env binding modes of each of the four vaccine-induced nAbs were distinct from previously known monoclonal HIV-1 neutralizing antibodies, but were nearly identical to each other. The similarities of these antibodies show that the immune system in outbred primates can respond to HIV-1 Env vaccination with a similar structural and genotypic solution for recognizing a particular neutralizing epitope. These results support rational vaccine design for HIV-1 that aims to reproducibly elicit, in genetically diverse primates, nAbs with specific paratope structures capable of binding conserved epitopes.

Research Organization:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES); USDOE Office of Science (SC), Biological and Environmental Research (BER); USDOD; National Institutes of Health (NIH)
Grant/Contract Number:
W-31-109-Eng-38; AC02-06CH11357; 89233218CNA000001; W81XWH-07-2-0067; R01- AI120801; UM1-AI100645; 5P30 AI064518; HHSN261200800001E
OSTI ID:
1797877
Alternate ID(s):
OSTI ID: 1786266; OSTI ID: 1827597
Report Number(s):
LA-UR-21-29267; 10.1371/journal.ppat.1009624
Journal Information:
PLoS Pathogens, Journal Name: PLoS Pathogens Vol. 17 Journal Issue: 6; ISSN 1553-7374
Publisher:
Public Library of Science (PLoS)Copyright Statement
Country of Publication:
United States
Language:
English

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